Modified presurgical nasoalveolar molding for patients with neonatal complete bilateral cleft lip and palate having a severely malpositioned premaxilla.

OBJECTIVE: To develop a modified presurgical nasoalveolar molding (MPNAM) with a premaxillary appliance, connected with two stainless steel wires and evaluate its therapeutic efficacy in newborns with complete bilateral cleft lip and palate (BCLP). METHOD: A total of 41 patients with neonatal complete BCLP having a severely protruded and deviated premaxilla were retrospectively selected from January 2017 to November 2019. All patients received the MPNAM device with a premaxillary appliance which was worn until cheilorrhaphy. Plaster casts from pre- and post-MPNAM treatments were scanned using a three-dimensional laser scanner, and the changes were recorded. Facial photographs of patients were taken during the treatment. RESULT: The average MPNAM treatment duration was 59.8 days. In all cases, the protrusive and deviated premaxilla was rapidly retracted and set into a suitable position after MPNAM treatment. The relative deviation distance and alveolar cleft width were significantly reduced. Both mid-palatal arch width and posterior arch width were increased. In addition, none of the patients developed any complications during the MPNAM treatment. CONCLUSION: Our MPNAM device was able to rapidly centralize the malpositioned premaxilla and reduce the alveolar cleft defect. This device can be applied in presurgical orthodontic treatments for patients with complete BCLP having a severely protruded and deviated premaxilla.

Charcot-Marie-Tooth 2B mutations in rab7 cause dosage-dependent neurodegeneration due to partial loss of function.

The small GTPase Rab7 is a key regulator of endosomal maturation in eukaryotic cells. Mutations in rab7 are thought to cause the dominant neuropathy Charcot-Marie-Tooth 2B (CMT2B) by a gain-of-function mechanism. Here we show that loss of rab7, but not overexpression of rab7 CMT2B mutants, causes adult-onset neurodegeneration in a Drosophila model. All CMT2B mutant proteins retain 10-50% function based on quantitative imaging, electrophysiology, and rescue experiments in sensory and motor neurons in vivo. Consequently, expression of CMT2B mutants at levels between 0.5 and 10-fold their endogenous levels fully rescues the neuropathy-like phenotypes of the rab7 mutant. Live imaging reveals that CMT2B proteins are inefficiently recruited to endosomes, but do not impair endosomal maturation. These findings are not consistent with a gain-of-function mechanism. Instead, they indicate a dosage-dependent sensitivity of neurons to rab7-dependent degradation. Our results suggest a therapeutic approach opposite to the currently proposed reduction of mutant protein function. DOI: http://dx.doi.org/10.7554/eLife.01064.001.